The overall goal of this research proposal is to understand the mechanism(s) by which estrogen affords neuroprotection within the hippocampus. The specific goal of this proposal focuses on the signaling intermediate Akt kinase, as Akt activation participates in neuronal survival and regulates other downstream neuronal survival markers such as CREB and Bcl-2. Preliminary data for this proposal indicates that estrogen can induce Akt activation and Bcl-2 mRNA production in a model of hippocampal neurons in vitro. Briefly, the Specific Aims of this Proposal are: (1) fully characterize this observed estrogen-mediated Akt activation in the hippocampus, (2) determine if estrogen activation of Akt precedes and potentially modulates an observed CREB activation, (c) determine if observed estrogen-stimulated Bcl-2 gene expression is associated with Akt activation in the hippocampus, and (4) determine if estrogen-enhanced neuronal survival to NMDA challenge is mediated by Akt. These Aims will characterize estrogen-initiated events which participate and potentially activate neuronal survival, form a molecular level to the hippocampus in vivo. This Proposal, therefore, is the logical extension from my prior graduate training to my current postdoctoral research position at Rockefeller University, where resident neuroanatomic expertise and animal facilities can provide for the investigations of complex, structural and functional analyses of the hippocampus in animal models.